Aage Andersen

BACKGROUND: Although second primary cancers are a leading cause of death among men with testicular cancer, few studies have quantified risks among long-term survivors. METHODS: Within 14 population-based tumor registries in Europe and North America (1943-2001), we identified 40,576 1-year survivors of testicular cancer and ascertained data on any new incident solid tumors among these patients. We used Poisson regression analysis to model relative risks (RRs) and excess absolute risks (EARs) of second solid cancers. All statistical tests were two-sided. RESULTS: A total of 2,285 second solid cancers were reported in the cohort. The relative risk and EAR decreased with increasing age at testicular cancer diagnosis (P < .001); the EAR increased with attained age (P < .001) but the excess RR decreased. Among 10-year survivors diagnosed with testicular cancer at age 35 years, the risk of developing a second solid tumor was increased (RR = 1.9, 95% confidence interval [CI] = 1.8 to 2.1). Risk remained statistically significantly elevated for 35 years (RR = 1.7, 95% CI = 1.5 to 2.0; P < .001). We observed statistically significantly elevated risks, for the first time, for cancers of the pleura (malignant mesothelioma; RR = 3.4, 95% CI = 1.7 to 5.9) and esophagus (RR = 1.7, 95% CI = 1.0 to 2.6). Cancers of the lung (RR = 1.5, 95% CI = 1.2 to 1.7), colon (RR = 2.0, 95% CI = 1.7 to 2.5), bladder (RR = 2.7, 95% CI = 2.2 to 3.1), pancreas (RR = 3.6, 95% CI = 2.8 to 4.6), and stomach (RR = 4.0, 95% CI = 3.2 to 4.8) accounted for almost 60% of the total excess. Overall patterns were similar for seminoma and nonseminoma patients, with lower risks observed for nonseminoma patients treated after 1975. Statistically significantly increased risks of solid cancers were observed among patients treated with radiotherapy alone (RR = 2.0, 95% CI = 1.9 to 2.2), chemotherapy alone (RR = 1.8, 95% CI = 1.3 to 2.5), and both (RR = 2.9, 95% CI = 1.9 to 4.2). For patients diagnosed with seminomas or nonseminomatous tumors at age 35 years, cumulative risks of solid cancer 40 years later (i.e., to age 75 years) were 36% and 31%, respectively, compared with 23% for the general population. CONCLUSIONS: Testicular cancer survivors are at statistically significantly increased risk of solid tumors for at least 35 years after treatment. Young patients may experience high levels of risk as they reach older ages. The statistically significantly increased risk of malignant mesothelioma in testicular cancer survivors has, to our knowledge, not been observed previously in a cohort of patients treated with radiotherapy.

Abstract A follow‐up study has revealed a clearly increased incidence of cancer of respiratory organs among men employed at a nickel refinery in Norway. During the period 1953–71 there were 48 cases of lung cancer, 14 cases of cancer of nasal sinuses and 5 cases of laryngeal cancer. The highest risk was among men involved in roasting, smelting and electrolysis. For these men the ratio of observed to expected number of cases was 7:1 for lung cancer and 40:1 for cancer of nasal sinuses. Still higher relative risks were found for workers of these categories whose employment had started before 1940. The refinery, established in 1910, practically discontinued production when the war hit Norway in 1940. Production was resumed in 1945, and subsequently the processes have undergone major changes. Of the 14 cases of cancer of nasal sinuses only one has occurred among men whose first employment started after 1945, but as the induction time for this form of cancer was found to be very long in this material, it is still uncertain whether a reduction of the risk has been achieved. As regards lung cancer, it is clear that the hazard of exposure still persisted around 1950. Although it has not been practicable in this study to obtain information on smoking habits and on possible exposure in other occupations, it is concluded that the increased risk among the men is largely ascribable to exposure at the refinery. Deaths and cases of cancer among the men were identified by computer linkage of past and current employees against all deaths in Norway and against all cases of cancer reported to the Cancer Registry of Norway during the follow‐up period.

To investigate the sensitivity of the CA 125 immunoradiometric assay for occult ovarian neoplasia, serum CA 125 levels were retrospectively determined "blind" in specimens collected from 105 women who subsequently developed ovarian neoplasia, and from 323 matched controls. The distribution of CA 125 levels was very different between the case and control populations (p = 0.0001) over the entire collection-to-diagnosis interval (range 1-143 months). Median CA 125 levels for all cases, and for those collected more than 24, 36 or even 60 months prior to diagnosis, were always 18 U/ml or greater, compared with a median of 10.9 U/ml for controls. Half of the cases collected within the 18 months preceding diagnosis had CA 125 levels of more than 30 U/ml and one-third had levels greater than 65 U/ml. About one-fourth of those collected prior to 60 months before diagnosis had levels above 30 U/ml. In contrast, approximately 7% and 0.9% of controls had levels in excess of 30 or 65 U/ml, respectively. Elevations occurred in cases eventually diagnosed with localized or advanced cancer, and with borderline or obviously malignant disease. These results provide an insight into the preclinical biology of ovarian neoplasia that may help in designing methods for early detection of this disease, and demonstrate the usefulness of the JANUS serum bank as a resource in evaluating serum tests.

BACKGROUND: The pattern of second cancers after treatment for cervical cancer provides important information on the risk of radiation-induced malignancies. Large numbers of women survive many years and can be studied for late effects. METHODS: Incident second cancers in 86,193 patients with cervical cancer reported to 13 population-based cancer registries in 5 countries were evaluated to estimate the risk of second cancer among very long term survivors. RESULTS: Overall, 7543 second cancers were observed versus 6015 cancers expected based on population rates (observed/expected = 1.2). Lung cancer accounted for nearly half of the excess cancers. Among the 49,828 women treated with radiation, 3750 survived 30 or more years and a two-fold risk of cancers of heavily irradiated organs was seen. Most of the excess cancers were of the rectum, vagina, vulva, ovary, and bladder. Patterns of risk over time since treatment were consistent with a radiation etiology. Significant increases of nonchronic lymphocytic leukemia and cancers of the bone and kidney were also linked to radiotherapy. Women treated surgically were also at significant risk of second cancers, in all likelihood related to cigarette smoking and risk factors similar to those of cervical cancer. CONCLUSIONS: Curative therapy for cervical cancer results in large numbers of long term survivors who develop second cancers very late in life. Radiation is an important cause of this increase and there is no evidence that risk returns to normal levels.